Burnham Institute's Cancer Center, which constitutes nearly 90% of the Institute's budget and personnel in La Jolla, CA, has been a recipient of the Cancer Center Support Grant continuously since 1981. The mission of the Cancer Center is to perform cutting-edge, collaborative basic research aimed towards understanding the pathogenesis of human cancer, and to promote the movement of basic research findings into novel strategies for cancer prevention, diagnosis, and therapy. Burnham's Cancer Center has continued on a strong trajectory since the last renewal. Burnham currently ranks 4"^ in NIH funding among all research institutes in the nation, and among top 20 organizations worldwide for its scientific impact measured by citations per publications. The Cancer Center has published >1,500 publications since the last renewal, of which 20% were collaborative. The Cancer Center has further enhanced its scientific prominence in the areas of cell adhesion, glycobiology, cancer genetics, cell signaling, and cell death research. Emerging areas of excellence include vascular biology and stem/progenitor cell biology in tumor development. An overarching theme of Chemical Biology has forged significant connections between our basic cancer research and the development of molecular probes and lead molecules for cancer therapy. 21 new faculty have been recruited since last renewal, bringing the number of full members to 56 (27% increase). Our grant base has increased by 60%, from $51 MM to $82MM, and collaborative grants constitute ~55% of all our NIH grant funding today, compared to 25% in 2003. Altogether, 44% of the Cancer Center's grants come from NCI and other cancer agencies. Through an in-depth planning and evaluation process, the Cancer Center has now a revised program structure, and consists of four highly collaborative and interdisciplinary Programs, named Tumor Microenvironment, Tumor Development, Signal Transduction, and Apoptosis &Cell Death Research. The Programs are buoyed by an underlying infrastructure that consists of 9 Shared Resources. Our enhanced Chemical Biology infrastructure not only aids the mission of our own scientists, but has also become a nation-wide resource supported by several grants and contracts from NIH and NCI. Going forward, our plans described in this application seek to further enhance our reputation in high-impact basic cancer biology, and to leverage our Chemical Biology Initiative to strengthen the linkage between our basic cancer research and our desire to make an increasingly substantial mark on the prevention, diagnosis, and treatment of cancer in the future.